Identifying heart failure patients suitable for resynchronization therapy using QRS complex width from an intracardiac electrogram

ABSTRACT

Methods and systems are disclosed for determining whether a patient is a responder to cardiac resynchronization therapy. The beginning and ending of the intrinsic ventricular depolarization are determined through signals measured from one or more electrodes implanted in the patient&#39;s heart. An interval between the beginning and ending of the intrinsic ventricular depolarization is computed and is compared to a threshold. The threshold may be determined empirically. The pacing parameters of a heart stimulation device, such as a pacemaker, may then be configured, for example, by setting the paced atrio-ventricular delay based on whether the patient responds positively to cardiac resynchronization therapy.

RELATED APPLICATIONS

[0001] The present application is a continuation-in-part of theapplication entitled METHOD AND APPARATUS FOR PREDICTING ACUTE RESPONSETO CARDIAC RESYNCHRONIZATION THERAPY, having U.S. Ser. No. 09/822,790filed on Mar. 30, 2001 and is also a continuation-in-part of theapplication entitled METHOD AND APPARATUS FOR DETERMINING THE CORONARYSINUS VEIN BRANCH ACCESSED BY A CORONARY SINUS LEAD, with U.S. Ser. No.09/822,638 also filed on Mar. 30, 2001.

TECHNICAL FIELD

[0002] The present invention is directed to cardiac resynchronizationtherapy. More specifically, the present invention is directed to methodsand systems for detecting whether patients are responders to ventricularresynchronization therapy.

BACKGROUND

[0003] The heart is a muscular organ comprising multiple chambers thatoperate in concert to circulate blood throughout the body's circulatorysystem. As shown in FIG. 1, the heart 100 includes a right-side portionor pump 102 and a left-side portion or pump 104. The right-side portion102 includes a right atrium 106 and a right ventricle 108. Similarly,the left-side portion 104 includes a left atrium 110 and a leftventricle 112. Oxygen-depleted blood returning to the heart 100 from thebody collects in the right atrium 106. When the right atrium 106 fills,the oxygen-depleted blood passes into the right ventricle 108 where itcan be pumped to the lungs (not shown) via the pulmonary arteries 117.Within the lungs, waste products (e.g., carbon dioxide) are removed fromthe blood and expelled from the body and oxygen is transferred to theblood. Oxygen-rich blood returning to the heart 100 from the lungs viathe pulmonary veins (not shown) collects in the left atrium 110. Thecircuit between the right-side portion 102, the lungs, and the leftatrium 110 is generally referred to as the pulmonary circulation. Whenthe left atrium 110 fills, the oxygen-rich blood passes into the leftventricle 112 where it can be pumped throughout the entire body. In sodoing, the heart 100 is able to supply oxygen to the body and facilitatethe removal of waste products from the body.

[0004] To circulate blood throughout the body's circulatory system asdescribed above, a beating heart performs a cardiac cycle that includesa systolic phase and a diastolic phase. During the systolic phase (e.g.,systole), the ventricular muscle cells of the right and left ventricles108, 112 contract to pump blood through the pulmonary circulation andthroughout the body, respectively. Conversely, during the diastolicphase (e.g., diastole), the ventricular muscle cells of the right andleft ventricles 108, 112 relax, during which the right and left atriums106, 110 contract to force blood into the right and left ventricles 108,112, respectively. Typically, the cardiac cycle occurs at a frequencybetween 60 and 100 cycles per minute and can vary depending on physicalexertion and/or emotional stimuli, such as, pain or anger.

[0005] The contractions of the muscular walls of each chamber of theheart 100 are controlled by a complex conduction system that propagateselectrical signals to the heart muscle tissue to effectuate the atrialand ventricular contractions necessary to circulate the blood. As shownin FIG. 2, the complex conduction system includes an atrial node 120(e.g., the sinoatrial node) and a ventricular node 122 (e.g., theatrioventricular node). The sinoatrial node 120 initiates an electricalimpulse that spreads through the muscle tissues of the right and leftatriums 106, 110 and the atrioventricular node 122. As a result, theright and left atriums 106, 110 contract to pump blood into the rightand left ventricles 108, 112 as discussed above. At the atrioventricularnode 122, the electrical signal is momentarily delayed beforepropagating through the right and left ventricles 108, 112. Within theright and left ventricles 108, 112, the conduction system includes rightand left bundle branches 126, 128 that extend from the atrioventricularnode 122 via the Bundle of His 124. The electrical impulse spreadsthrough the muscle tissues of the right and left ventricles 108, 112 viathe right and left bundle branches 126, 128, respectively. As a result,the right and left ventricles 108, 112 contract to pump blood throughoutthe body as discussed above.

[0006] Normally, the muscular walls of each chamber of the heart 100contract synchronously in a precise sequence to efficiently circulatethe blood as described above. In particular, both the right and leftatriums 106, 110 contract (e.g., atrial contractions) and relaxsynchronously. Shortly after the atrial contractions, both the right andleft ventricles 108, 112 contract (e.g., ventricular contractions) andrelax synchronously. Several disorders or arrhythmias of the heart canprevent the heart from operating normally, such as, blockage of theconduction system, heart disease (e.g., coronary artery disease),abnormal heart valve function, or heart failure.

[0007] Blockage in the conduction system can cause a slight or severedelay in the electrical impulses propagating through theatrioventricular node 122, causing inadequate ventricular relaxationsand filling. In situations where the blockage is in the ventricles(e.g., the right and left bundle branches 126, 128), the right and/orleft ventricles 108, 112 can only be excited through slow muscle tissueconduction. As a result, the muscular walls of the affected ventricle(108 and/or 112) do not contract synchronously (e.g., asynchronouscontraction), thereby, reducing the overall effectiveness of the heart100 to pump oxygen-rich blood throughout the body. For example,asynchronous contraction of the left ventricular muscles can degrade theglobal contractility (e.g., the pumping power) of the left ventricle 112which can be measured by the peak ventricular pressure change duringsystole (denoted as “LV+dp/dt”). A decrease in LV+dp/dt corresponds to aworsened pumping efficiency and less cardiac output.

[0008] Similarly, heart valve disorders (e.g., valve regurgitation orvalve stenosis) can interfere with the heart's 100 ability to pumpblood, thereby, reducing stroke volume (i.e., aortic pulse pressure)and/or cardiac output.

[0009] Various medical procedures have been developed to address theseand other heart disorders. In particular, cardiac resynchronizationtherapy (“CRT”) can be used to improve the conduction pattern andsequence of mechanical contractions of the heart. CRT involves the useof an artificial electrical stimulator that is surgically implantedwithin the patient's body. Leads from the stimulator can be affixed at adesired location within the heart to effectuate synchronous atrialand/or ventricular contractions. Typically, the location of the leads(e.g., stimulation site) is selected based upon the severity and/orlocation of the blockage. Electrical stimulation signals can bedelivered to resynchronize the heart, thereby, improving cardiacperformance.

[0010] Despite these advantages, several shortcomings exist that limitthe usefulness of CRT. For example, results from many clinical studieshave shown that hemodynamic response to CRT typically varies frompatient to patient, ranging from very positive (e.g., improvement) tosubstantially negative (e.g., deterioration). Thus, in order to predictthe benefit from CRT, the patient typically must be screened prior toreceiving the therapy. One common method that predicts hemodynamicresponse to CRT relies on measurement of a surface electrocardiagram(ECG). Such measurement is often performed manually and is subject tohuman error. Additionally, it is difficult to implement such a surfacemeasurement with an implantable device thereby making it difficult tocontinuously monitor the response.

[0011] Thus, there is a need for improved methods and systems that canautomatically and reliably predict whether a patient will have apositive response to CRT and/or be able to monitor the responsecontinuously during the entire course of CRT.

SUMMARY

[0012] Embodiments of the present invention provide methods and systemsthat detect whether a patient is a responder to CRT. The methods andsystems involve making measurements with at least one electrodeimplanted within the patient's heart. An implanted heart stimulationdevice, external device programmer, or other device may then determinefrom the measurements whether the patient will have a positive responseto CRT.

[0013] The present invention may be viewed as a method for determiningwhether a patient is a responder to resynchronization therapy. Themethod involves detecting a beginning of an intrinsic ventriculardepolarization with an electrode positioned at a ventricle of the heartof the patient. An ending of the intrinsic ventricular depolarization isalso detected. An interval between the beginning of the intrinsicventricular depolarization and the ending of the intrinsic ventriculardepolarization is measured. The interval is then compared to athreshold.

[0014] The present invention may also be viewed as a system fordetermining whether a patient is a responder to resynchronizationtherapy. The system includes an electrode positioned at a ventricle ofthe heart of the patient. A detection module is communicatively linkedto the electrode, and the detection module detects a beginning of anintrinsic ventricular depolarization and an ending of the intrinsicventricular depolarization. The system also includes a processing modulecommunicatively linked to the detection module, wherein the processingmodule computes an interval between the beginning of the intrinsicventricular depolarization and the ending of the intrinsic ventriculardepolarization and compares the interval to a threshold.

[0015] The present invention may also be viewed as another system fordetermining whether a patient is a responder to resynchronizationtherapy. The system includes means for detecting a beginning of anintrinsic ventricular depolarization and an ending of the intrinsicventricular depolarization. Additionally, the system includes means forcomputing an interval between the beginning of the intrinsic ventriculardepolarization and the ending of the intrinsic ventriculardepolarization and for comparing the interval to a threshold.

DESCRIPTION OF THE DRAWINGS

[0016]FIG. 1 is a diagram showing the various chambers of the heart.

[0017]FIG. 2 is a diagram showing the various chambers and theelectrical conduction system of the heart.

[0018]FIG. 3 is a graph showing ventricular depolarization as a functionof time.

[0019] FIGS. 4-6 are diagrams illustrating a heart and the electricalconduction system advancing through a normal cardiac cycle.

[0020]FIG. 7 is a graph illustrating mean percentage change in leftventricular pressure (LV+dp/dt) resulting from application of CRTplotted against the duration of intrinsic ventricular depolarization forresponders and non-responders.

[0021]FIG. 8 is a graph illustrating the accuracy, sensitivity, andspecificity of the separation between responders and non-responders forvarious thresholds of ventricular depolarization duration used to makethe distinction.

[0022]FIG. 9 illustrates one possible embodiment of a system that can beused to detect whether a patient is a responder to CRT.

[0023]FIG. 10 is an operational flow summarizing the logical operationsemployed by an exemplary system for detecting whether a patient is aresponder to CRT.

DETAILED DESCRIPTION

[0024] Various embodiments of the present invention will be described indetail with reference to the drawings, wherein like reference numeralsrepresent like parts and assemblies throughout the several views.Reference to various embodiments does not limit the scope of the presentinvention, which is limited only by the scope of the claims attachedhereto.

[0025] The following discussion is intended to provide a brief, generaldescription of a suitable method for predicting whether a patient willpositively respond to cardiac resynchronization therapy (“CRT”). As willbe described in greater detail below, the method of the presentdisclosure predicts a patient's response to CRT by measuring andcomparing an intrinsic ventricular depolarization period against athreshold. As will become apparent from the discussion below inconnection with the various drawings, the ventricular depolarizationperiod may be measured by finding a beginning and ending of thedepolarization through processing of an intracardiac signal to find abeginning value Q* and an ending value S*. However, those of ordinaryskill in the art will readily appreciate that the method of the presentdisclosure can be implemented using any suitable beginning and endingvalue, which may or may not be found by employing various methods formeasuring Q* and S*.

[0026] In a preferred embodiment, the method of the present disclosurepredicts whether a patient will respond to CRT by evaluating the periodof depolarization of the right or left ventricles 108, 112 (FIG. 1). Theperiod of depolarization of the ventricles 108, 112 can be evaluatedusing an intracardiac electrogram. An intracardiac electrogram isgenerally a graphical depiction of the electrical depolarization orexcitement of the heart 100 (FIG. 1) that is measured by one or moreelectrodes placed on or within the heart 100, such as within the rightor left ventricles.

[0027] An exemplary electrogram for an intrinsic systolic cycle is shownin FIG. 3. Each portion of the electrogram is typically given analphabetic designation corresponding to a predetermined period ofelectrical depolarization or excitement. For example, the portion of theelectrogram that represents atrial depolarization is commonly referredto as the P-wave (not shown). Similarly, the portion of the electrogramthat represents ventricular depolarization is commonly referred to asthe QRS complex comprising a Q-wave, an R-wave, and an S-wave. Moreover,the portion of the electrogram that represents ventricular recovery orrepolarization is commonly referred to as the T-wave (not shown).

[0028] As shown in FIG. 3, the QRS complex has a beginning and anending. To determine the beginning and ending, the intracardiacelectrogram may be analyzed, as discussed below, to find variousrepresentative values. The representative beginning value Q* and endingvalue S* are shown in FIG. 3. Other values representative of thebeginning and ending of the QRS complex may be used in place of the Q*and S* values that are defined by the calculations discussed below.

[0029] Each period of electrical depolarization or excitementrepresented on the electrogram corresponds to a period of muscularactivation within the heart 100 (FIG. 1). FIGS. 4-6 are schematicillustrations depicting the various periods of muscular activationwithin the heart 100. As shown in FIGS. 4-6, the electrogram data can bemonitored using any suitable electrocardiographic device 150, such as animplantable heart stimulation device (i.e. CRT device), that isconnected to leads located on or within the heart 100.

[0030]FIG. 4 is a schematic illustration showing the period of atrialactivation in response to electrical impulses initiated at thesinoatrial node 120 (corresponding to the P-wave portion as discussedabove). After electrical impulses spread from the sinoatrial node 120,the muscle tissues of the right and left atriums 106, 110 contract topump blood into the right and left ventricles 108, 112, respectively.

[0031]FIG. 5 is a schematic illustration showing the period of aventricular depolarization in response to electrical impulses initiatedat the atrioventricular node 122 that spread through the ventricles 108,112 (corresponding to the QRS portion as discussed above). Afterelectrical impulses spread from the atrioventricular node 122, themuscle tissues of the right and left ventricles 108, 112 contract topump blood to the lungs and throughout the body, respectively.

[0032]FIG. 6 is a schematic illustration showing ventricular recovery orrepolarization (corresponding to the T-wave portion as discussed above).During ventricular repolarization, the membrane potential of the musclecells reverse polarity and return to their resting state, thereby,causing the ventricles to relax.

[0033] An electrogram of a patient's heart can be used to assess cardiacperformance by validating the existence of cardiac abnormalities, suchas, arrhythmias evinced by an abnormally fast heart rate (e.g.,tachycardia), an abnormally slow heart rate (e.g., bradycardia), or anormal rate but the depolarization is abnormally propagated (e.g.,ectopic, or conduction system defect). The existence of an arrhythmiatypically indicates that the heart's rhythm initiation and/or conductionsystem is functioning abnormally. CRT can be used, among otherapplications, to treat abnormal electrical conduction. In particular,CRT can be used to deliver electrical stimulation to portions of theheart 100 (FIG. 1) to resynchronize the heart's activation, thereby,improving the efficiency of atrial and ventricular contractionsnecessary to circulate blood throughout the body. The amount of benefitderived from CRT, however, typically varies depending upon the severityof the abnormality of the heart's conduction system. Therefore, prior totreating a patient using CRT, it is preferable to evaluate whether theheart's 100 (FIG. 1) conduction system is normal or abnormal.

[0034] The heart's ventricular conduction system can be assessed throughanalysis of the duration of ventricular depolarization. Identificationof patients who may have a positive response to CRT can be performedusing the duration of ventricular depolarization (e.g., the width of theQRS complex as shown in FIG. 3) measured from an intracardiacelectrogram. For example, if the duration of ventricular depolarizationis greater than a given threshold, then the patient may be considered aresponder to CRT, and the CRT device for that patient may be configuredappropriately. Patients are referred to as responders because they havean abnormal conduction system that can benefit from CRT.

[0035] Once the patient has been deemed a responder or non-responder,the CRT device can be configured to stimulate the heart to produce anatrioventricular delay of a duration appropriate for the patient type asis discussed below. For responders, the atrioventricular delay isgenerally set to about one-half of the intrinsic, or naturally occurringatrioventricular delay. For non-responders, the atrioventricular delayis set to approximately the intrinsic atrioventricular delay, such asthe intrinsic atrioventricular delay minus a relatively small delayfactor of about 30 milliseconds. One with ordinary skill in the art willrecognize that other atrioventricular delay settings for responders andnon-responders are possible as well. The atrioventricular delay isgenerally considered to be the length of time between an atrial sensed(or stimulated) event and the delivery of a ventricular output pulse.

[0036]FIG. 7 shows a graph of the mean percent change in peak leftventricle pressure “LV dp/dt” after application of CRT over threeatrioventricular delays for a group consisting of both responders andnon-responders. Responders may be defined as those who receive anincrease in peak left ventricle pressure when CRT is applied. From thegraph, one can see that a relationship exists between the intrinsic Q*S*depolarization interval and the increase in peak left ventricle pressuredue to CRT. For those having a relatively long intrinsic ventriculardepolarization, CRT caused a relatively large increase in peak leftventricle pressure. For those having a relatively short intrinsicventricular depolarization, CRT caused a relatively small increase or insome instances a decrease in peak left ventricle pressure.

[0037] A linear regression of the test cases shows that the correlationof percent change in peak left ventricle pressure to Q*S* is defined bythe equation y=0.3462x −51.807, with a coefficient of determinationR²=0.3974. The vertical line of FIG. 7 indicates that an appropriateQ*S* threshold for distinguishing responders from non-responders isapproximately 175 milliseconds for humans. The determination of 175milliseconds as an appropriate threshold is further supported by theplot in FIG. 8.

[0038]FIG. 8 shows the values for the accuracy which represents theprobability of correct classification of either a responder ornon-responder, sensitivity which represents the probability of correctclassification of patients as responders, and specificity which is theprobability of correct classification of patients as non-respondersplotted against Q*S* thresholds for humans. From this plot, it can beseen that the optimal threshold is about 175 milliseconds for humansbecause at this point the accuracy and sensitivity are above 0.95 andthe specificity is above 0.88.

[0039] One possible embodiment of a CRT system 300 that can be used toimplement the methods for determining whether a patient is a responderis illustrated in FIG. 9. As shown in FIG. 9, the CRT system 300generally comprises a programming device 301 that can be used toregulate stimulation pulses that are delivered to the heart 100. In onepossible embodiment, the heart 100 is connected to various leads 320having electrodes (not shown) and terminal pins (not shown) that canconnect the heart 100 to the CRT system 300. The various leads 320connecting the heart 100 to the CRT system 300 will be described ingreater detail below.

[0040] The programmer 301 can regulate the stimulation pulses deliveredto the heart 100 using, for example, a telemetry module 302. In onepossible embodiment, the telemetry module 302 is unidirectional (e.g.,capable of allowing the programmer 301 to receive data). However, in analternative embodiment, the telemetry module 302 is bi-directional(e.g., capable of allowing the programmer 301 to receive and/or senddata). The command input module 304 is configured to interpret the datareceived from the programmer 301 such that the stimulation pulses can beaccurately distributed according to predetermined criteria, such as, thespecific requirements of the patient being treated.

[0041] A controller 306 can be used to control the specific instructionsregarding the stimulation pulses delivered to the heart 100. In onepossible embodiment, the controller 306 can be controlled manually. Inan alternative embodiment, however, the controller 306 can be controlledautomatically using, for example, feedback received from an intrinsicsignal analyzer 338. Moreover, one having ordinary skill in the art willreadily appreciate that the controller 306 and the programmer 301 can becombined into a single unit. The instructions from the controller 306are received by an electrode switching and output circuitry module 308that delivers the stimulation pulses to the appropriate lead 320 withinthe heart 100.

[0042] As discussed above, the heart 100 is connected to the CRT system300 using various leads 320. The various leads 320 are preferablyconfigured to carry the CRT stimuli from the CRT device to the heart100. Moreover, the various leads 320 can likewise operate in a demandmode, thereby, relaying intrinsic cardiac signals from the heart's 100electrical conduction system back to one or more sense amplifiers 310,312, 314, 316. In one possible embodiment, the various leads 320comprise separate and distinct leads connecting the CRT system 300 todifferent portions of the heart 100. In particular, the various leads320 can comprise a lead 322 connected to the right-side portion or pump102 (FIG. 1) of the heart 100, including, for example, a right atriumlead 324 configured to operate with a right atrium amplifier 310 and aright ventricle lead 326 configured to operate with a right ventricleamplifier 312. Similarly, the various leads 320 can comprise a lead 327connected to the left-side portion or pump 104 (FIG. 1) of the heart100, including, for example, a first left ventricle lead 328 configuredto operate with a first left ventricle amplifier 314 and a second leftventricle lead 330 configured to operate with a second left ventricleamplifier 316.

[0043] As discussed above, the various leads 320 connected to the heart100 can relay intrinsic cardiac signals from the heart's 100 electricalconduction system back to the one or more sense amplifiers 310, 312,314, 316. The intrinsic cardiac signals amplified by the senseamplifiers 310, 312, 314, 316 can then be processed by an intrinsicsignal analyzer 338 incorporated in whole or in part by an implantableheart stimulation device (i.e., CRT device) or a device programmer. Theintrinsic signal analyzer 338 generally can comprise a detection module340 that is configured to analyze the intracardiac electrograminformation to detect the beginning and ending of ventriculardepolarization, such as the Q* and S* values discussed above withreference to FIG. 3.

[0044] Calculating Q* and S* from the intracardiac electrogram signalmay be done in various ways. See for example, the calculation of Q* fromU.S. Pat. No. 6,144,880, which is commonly assigned to CardiacPacemakers, Inc. and is incorporated herein by reference. In oneembodiment, calculating Q* and S* may proceed as follows. For Q*, awaveform V(n) including the QRS complex must be acquired and analyzed,such as by the detection module 340 of the CRT device or CRT deviceprogrammer. The acquisition involves digitizing the waveform V(n)including the activity beginning at the time of an atrial referencemarker indicating the end of atrial activity and extending beyond theQRS complex received by the electrode in the left or right ventricle andstoring it in memory of the CRT device or CRT device programmer. Then,Q* is found by the following process.

[0045] First, the detection module 340 smooths the waveform V(n). Thismay be done by smoothing the waveform V(n) seven times using a 5 pointrectangular moving window (for a sampling frequency of 500 Hz) wherebythe 5 samples for each window are averaged and the average is assignedto the middle sample of the five. A derivative dV(n)/dt of the smoothedwaveform is taken, and the absolute value of the derivative dV(n)/dt isnormalized to range from 0 to 1.

[0046] The time samples n from the atrial reference marker time T_(p) tothe time T_(R) of the peak of the R wave of the QRS complex areanalyzed. This analysis involves calculating the mean and standarddeviation of both the smoothed waveform V(n) and the normalized absolutevalue of its derivative dV(n)/dt for each time sample within a 50 msmoving window. The baseline window with the minimum mean (i.e., baselinemean) plus a baseline standard deviation for |dv(n)/dt| is found and itsvalues are used in the following steps.

[0047] For each sample n between T_(p) and T_(R) if the baseline mean isless than |dV(n)/dt|, but more than or equal to |dV(n)/dt|, then thenumber of data points N in another 50 ms window is found. N is theaccumulation of each data point /nw where |dv(nw)/dt| is greater thanthe baseline mean plus the baseline standard deviation. The windowsample nw of this other window ranges from n to n plus the total numberof data points in the window.

[0048] If N divided by the total number of data points in the window isgreater than 0.96 and T_(q)=0, then set T_(q) equal to n0−1, where T_(q)is the current result of sample time for Q* and n0 is the time sample ofthe first data point that contributes to N. If the total number of datapoints in the window minus N is greater than or equal to 2, then T_(q)is reset to zero. After this is completed for all values of n betweenT_(p) and T_(R), then the final value of T_(q) is used as Q*. Thisprocess may be repeated to obtain a value of Q* for several beats, suchas 16, and the median of these Q* values may be used in the computationof the ventricular depolarization interval. It may be desirable toinclude Q* values in the median determination for beats where theinterval from R wave peak to R wave peak between beats has a variationwithin 10%.

[0049] For S*, the same process may be repeated but the time samples nranging from the time T_(p)+1 which occurs after sensing atrial activityin the next cycle until the time T_(R) of the peak of the R wave of theQRS complex of the current cycle are analyzed rather than the samplesoccurring prior to the R wave peak. Once the process discussed above hasbeen completed for all values starting at T_(p)+1 and continuing toT_(R) (i.e., working backwards through the samples with respect totime), the final value of T_(q) is used as S*. As with Q*, this processfor S* may be repeated to obtain a value of S* for several beats, suchas 16, and the median of these S* values may be used in the computationof the ventricular depolarization interval.

[0050] After analysis of the electrogram information to find thebeginning and ending of ventricular depolarization such as Q* and S*, aprocessing module 342 may compute the duration of depolarization andcompare it to a threshold value, such as 175 milliseconds, in accordancewith the method described below with reference to FIG. 10 to validatethe patient as a responder or non-responder. A configuration module 344can be used to make adjustments to the CRT system 300 based upon whetherthe processing module 342 determines the patient to be a responder ornon-responder. The adjustments may include setting the atrioventriculardelay of the CRT device to about one-half of the intrinsic value forresponders or to approximately the intrinsic value for non-responders.For embodiments where the device programmer includes all or part of theintrinsic signal analyzer 338, the device programmer may send aninstruction through telemetry 302 to the implanted heart stimulationdevice to set the atrioventricular delay.

[0051] The method of the present disclosure can be implemented using aCRT system as shown in FIG. 9 comprising various devices and/orprogrammers, including implantable or external CRT devices and/orprogrammers such as a CRT tachy or brady system. Accordingly, the methodof the present disclosure can be implemented as logical operationscontrolling a suitable CRT device and/or programmer. The logicaloperations of the present disclosure can be implemented: (1) as asequence of computer implemented steps running on the CRT device and/orprogrammer; and (2) as interconnected machine modules within the CRTdevice and/or programmer.

[0052] The implementation is a matter of choice dependant on theperformance requirements of the CRT device and/or programmerimplementing the method of the present disclosure and the componentsselected by or utilized by the users of the method. Accordingly, thelogical operations making up the embodiments of the method of thepresent disclosure described herein can be referred to variously asoperations, steps, or modules. It will be recognized by one of ordinaryskill in the art that the operations, steps, and modules may beimplemented in software, in firmware, in special purpose digital logic,analog circuits, and any combination thereof without deviating from thespirit and scope of the present invention as recited within the claimsattached hereto.

[0053]FIG. 10 shows an exemplary embodiment 346 of the logicaloperations of the processing module 342. The process begins by theprocessing module 342 receiving the Q* and S* values from the signalsmeasured by detection module 340 at receive operation 348. At intervaloperation 350, the processing module 342 computes the time intervalbetween the Q* and S* values. At query operation 352, the processingmodule 342 compares the Q*S* interval to the threshold, such as 175milliseconds.

[0054] If the processing module 342 determines that Q*S* is greater thanthe threshold, then the processing module 342 selects anatrioventricular delay that is about one-half of the intrinsicatrioventricular delay at delay operation 354. If the processing module342 determines that Q*S* is less than or equal to the threshold, thenthe processing module 342 selects an atrioventricular delay that isapproximately equal to the intrinsic atrioventricular delay at delayoperation 356. It is desirable at delay operation 356 to set theatrioventricular delay to the intrinsic atrioventricular delay valueless a small delay factor of about 30 milliseconds. The configurationmodule 344 then implements the atrioventricular delay selected byprocessing module 342 when applying CRT or other pacing therapy to thepatient.

[0055] While the invention has been particularly shown and describedwith reference to preferred embodiments thereof, it will be understoodby those skilled in the art that various other changes in the form anddetails may be made therein without departing from the spirit and scopeof the invention.

What is claimed is:
 1. A method for determining whether a patient is aresponder to resynchronization therapy, the method comprising: detectinga beginning of an intrinsic ventricular depolarization with an electrodepositioned at a ventricle of the heart of the patient; detecting anending of the intrinsic ventricular depolarization; measuring aninterval between the beginning of the intrinsic ventriculardepolarization and the ending of the intrinsic ventriculardepolarization; and comparing the interval to a threshold.
 2. The methodof claim 1, wherein the electrode that detects the beginning of theintrinsic ventricular depolarization detects the ending of the intrinsicventricular depolarization.
 3. The method of claim 1, wherein theelectrode is positioned within a left ventricle.
 4. The method of claim1, wherein the threshold is 175 milliseconds.
 5. The method of claim 1,wherein a heart stimulation device is electrically connected to theelectrode, the method further comprising: when the interval is greaterthan the threshold, setting a paced atrio-ventricular delay of the heartstimulation device to less than an intrinsic atrio-ventricular delay ofthe patient.
 6. The method of claim 5, wherein the pacedatrio-ventricular delay of the heart stimulation device is set toapproximately one-half the intrinsic atrio-ventricular delay of thepatient.
 7. The method of claim 5, further comprising the step of: whenthe interval is less than the threshold, setting the pacedatrio-ventricular delay of the heart stimulation device equal toapproximately 30 milliseconds less than the intrinsic atrio-ventriculardelay of the patient.
 8. The method of claim 5, wherein the heartstimulation device performs the step of measuring the interval.
 9. Themethod of claim 5, wherein the heart stimulation device performs thestep of comparing the interval to the threshold.
 10. The method of claim5, wherein a device programmer is in communication with the heartstimulation device, the method further comprising: sending aninstruction to the heart stimulation device to set the pacedatrioventricular delay of the heart stimulation device.
 11. The methodof claim 1, wherein a device programmer is in communication with theelectrode, and wherein the device programmer performs the step ofmeasuring the interval.
 12. The method of claim 9, wherein the deviceprogrammer performs the step of comparing the interval to the threshold.13. The method of claim 1, wherein measuring an interval comprisesstatistical analysis of multiple intervals measured from multipleintrinsic ventricular depolarizations.
 14. The method of claim 13,wherein the statistical analysis involves calculating a median of themultiple intervals.
 15. The method of claim 1, wherein detecting thebeginning and ending of the ventricular depolarization comprisesdetecting Q* and S*.
 16. The method of claim 15, wherein Q* is computedby smoothing a depolarization signal and finding a point in time in acardiac cycle prior to an R wave peak where a value of the smootheddepolarization first exceeds a baseline standard deviation valuecomputed from the smoothed waveform and wherein S* is computed byfinding a point in time after the R wave peak where a value of thesmoothed depolarization last exceeds the baseline standard deviationvalue.
 17. The method of claim 1, wherein the steps of detecting thebeginning and the ending of the intrinsic ventricular depolarization,measuring the interval, and comparing the interval are performed by animplantable device.
 18. The method of claim 1, wherein the steps ofdetecting the beginning and the ending of the intrinsic ventriculardepolarization, measuring the interval, and comparing the interval areperformed periodically other than for each cardiac cycle.
 19. A systemfor determining whether a patient is a responder to resynchronizationtherapy, the system comprising: an electrode positioned at a ventricleof the heart of the patient; a detection module communicatively linkedto the electrode, wherein the detection module detects a beginning of anintrinsic ventricular depolarization and an ending of the intrinsicventricular depolarization; and a processing module communicativelylinked to the detection module, wherein the processing module computesan interval between the beginning of the intrinsic ventriculardepolarization and the ending of the intrinsic ventriculardepolarization and compares the interval to a threshold.
 20. The systemof claim 19, wherein the detection module detects the beginning of theintrinsic ventricular depolarization and the ending of the intrinsicventricular depolarization from an electrical signal received from theelectrode.
 21. The system of claim 19, wherein the electrode ispositioned within a left ventricle.
 22. The system of claim 19, whereinthe threshold is 175 milliseconds.
 23. The system of claim 19, whereinthe detection module and processing module are contained in a heartstimulation device that is electrically connected to the electrode, andwherein when the interval is greater than the threshold, the heartstimulation device sets a paced atrio-ventricular delay to less than anintrinsic atrioventricular delay of the patient.
 24. The system of claim23, wherein the paced atrio-ventricular delay is set to one-half of theintrinsic atrio-ventricular delay of the patient.
 25. The system ofclaim 23, wherein when the interval is less than the threshold, theheart stimulation device sets the paced atrio-ventricular delay toapproximately 30 milliseconds less than the intrinsic atrio-ventriculardelay.
 26. The system of claim 19, wherein the detection module andprocessing module are contained in a device programmer that is incommunication with a heart stimulation device that is electricallyconnected to the electrode, and wherein the device programmer sends aninstruction to the heart stimulation device to set the pacedatrio-ventricular delay of the heart stimulation device.
 27. The systemof claim 19, wherein the processing module statistically analyzesmultiple intervals detected from multiple intrinsic ventriculardepolarizations.
 28. The system of claim 27, wherein the statisticalanalysis involves calculating a median of the multiple intervals. 29.The system of claim 19, wherein the beginning of the ventriculardepolarization is Q* and the ending of the ventricular depolarization isS*.
 30. The system of claim 29, wherein Q* is computed by smoothing adepolarization signal and finding a point in time in a cardiac cycleprior to an R wave peak where a value of the smoothed depolarizationfirst exceeds a baseline standard deviation value computed from thesmoothed waveform and wherein S* is computed by finding a point in timeafter the R wave peak where a value of the smoothed depolarization lastexceeds the baseline standard deviation value.
 31. The system of claim19, wherein the detection module and the processing module are containedin an implantable device.
 32. The system of claim 19, wherein thedetection module detects the beginning and ending of the ventriculardepolarization and the processing module computes the interval andcompares the interval to a threshold periodically other than for eachcardiac cycle.
 33. A system for determining whether a patient is aresponder to resynchronization therapy, the system comprising: means fordetecting a beginning of an intrinsic ventricular depolarization and anending of the intrinsic ventricular depolarization; and means forcomputing an interval between the beginning of the intrinsic ventriculardepolarization and the ending of the intrinsic ventriculardepolarization and for comparing the interval to a threshold.
 34. Thesystem of claim 33, wherein the means for detecting detects thebeginning of the intrinsic ventricular depolarization and the ending ofthe intrinsic ventricular depolarization from an electrical signalreceived from an electrode positioned at a ventricle.
 35. The system ofclaim 33, wherein the electrode is positioned within a left ventricle.36. The system of claim 33, wherein the threshold is 175 milliseconds.37. The system of claim 34, wherein the means for detecting and themeans for computing and for comparing are contained in a heartstimulation device that is electrically connected to the electrode, andwherein when the interval is greater than the threshold, the heartstimulation device sets a paced atrio-ventricular delay to less than anintrinsic atrio-ventricular delay of the patient.
 38. The system ofclaim 37, wherein the paced atrio-ventricular delay is set to one-halfof the intrinsic atrio-ventricular delay of the patient.
 39. The systemof claim 37, wherein when the interval is less than the threshold, theheart stimulation device sets the paced atrio-ventricular delay to equalto approximately 30 milliseconds less than the intrinsicatrio-ventricular delay of the patient.
 40. The system of claim 33,wherein the means for detecting and the means for computing and forcomparing are contained in a device programmer that is in communicationwith a heart stimulation device, and wherein the device programmer sendsan instruction to the heart stimulation device to set the pacedatrio-ventricular delay of the heart stimulation device.
 41. The systemof claim 33, wherein the means for computing and for comparing computesthe interval by statistically analyzing multiple intervals detected frommultiple intrinsic ventricular depolarizations.
 42. The system of claim41, wherein the means for computing and for comparing statisticallyanalyzes multiple intervals by calculating a median.
 43. The system ofclaim 33, wherein the beginning of the ventricular depolarization is Q*and the ending of the ventricular depolarization is S*.
 44. The systemof claim 43, wherein Q* is computed by smoothing a depolarization signaland finding a point in time in a cardiac cycle prior to an R wave peakwhere a value of the smoothed depolarization signal first exceeds abaseline standard deviation value computed from the smootheddepolarization signal and wherein S* is computed by finding a point intime after the R wave peak where a value of the smoothed depolarizationsignal last exceeds the baseline standard deviation value.
 45. Thesystem of claim 33, wherein the means for detecting and the means forcomputing and comparing are contained in an implantable device.
 46. Thesystem of claim 33, wherein the means for detecting detects thebeginning and ending of the ventricular depolarization and the means forcomputing and comparing computes the interval and compares the intervalto a threshold periodically other than for each cardiac cycle.